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MRI and PET Biomarkers for Cognitive Decline in Older Adults

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ClinicalTrials.gov Identifier: NCT03860857
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : November 4, 2020
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Michael Yassa, University of California, Irvine

Tracking Information
First Submitted Date  ICMJE February 15, 2019
First Posted Date  ICMJE March 4, 2019
Last Update Posted Date November 4, 2020
Actual Study Start Date  ICMJE May 1, 2018
Estimated Primary Completion Date December 22, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
Change in Clinical Dementia Rating - Sum of Box Score [ Time Frame: Years 4 and 5 of the grant ]
A measure of cognitive/clinical decline
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
  • Change in lure discrimination index - objects [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of performance on the object pattern separation task
  • Change in lure discrimination index - spatial [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of performance on the spatial pattern separation task
  • Change in lure discrimination index - temporal [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of performance on the temporal pattern separation task
  • Change in entorhinal cortical thickness [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of structural decline on MRI scans
  • Change in perforant path integrity [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of structural connectivity decline on MRI scans
  • Change in tau spatial distribution - advancing Braak stage [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of tau spatial spread on tau PET scans
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MRI and PET Biomarkers for Cognitive Decline in Older Adults
Official Title  ICMJE MRI and PET Biomarkers for Cognitive Decline in Older Adults
Brief Summary The purpose of this research study is to understand the factors that underlie changes in thinking and memory with increasing age. The investigators will test the usefulness of MRI, PET, and cognitive testing in detecting subtle changes in the brain that precede cognitive decline. An addendum to this study includes additional PET scans to examine the relationship between tau protein in the brain and cognitive decline. Tau is a protein that is known to form tangles in the areas of the brain important for memory, and these tau tangles are a hallmark of Alzheimer's disease. This sub-study research aims to look at the tau accumulation in the brain using an investigational drug called MK-6240, which is a radio tracer that gets injected prior to a positron emission tomography (PET) scan.
Detailed Description This study investigates the relationship between Alzheimer's disease (AD) pathology, brain structure and function, as well as cognition in non-demented older adults. The goal is to develop a more complete understanding of the factors that lead to cognitive decline in the elderly and progression to AD. The investigators will enroll 200 cognitively intact adults between the ages of 60-85 years old from the UCI Alzheimer's Disease Research Center or directly from the local community. Study procedures will include: 1) PET amyloid scans with Amyvid™ radiotracer (florbetapir-F18) and PET tau scans with [18F]MK6240 radiotracer; 2) High-resolution structural, functional, and diffusion MRI; and 3) Cognitive examinations. The investigators will track cognitive outcomes through longitudinal monitoring. Amyloid imaging will only be conducted once in the study at baseline, and MRI and tau PET imaging will be at baseline and Year 1. The investigators aim to identify the best combination of tests for predicting longitudinal cognitive/clinical decline. The proposed study will significantly inform the understanding of cognitive decline in the aging brain and allow investigators to better define preclinical AD and make recommendations for future intervention trials.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
All participants will complete the same study procedures, including the tau PET scans with investigational radio tracer 18F-MK6240. The arms define the age range and APOE status of the participants, with each having their own enrollment target.
Masking: None (Open Label)
Primary Purpose: Health Services Research
Condition  ICMJE
  • Alzheimer Disease
  • Cognitive Impairment
  • Cognitive Decline
Intervention  ICMJE
  • Radiation: Amyloid PET scan
    Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18
  • Drug: Tau PET scan using MK-6240
    Tau Positron Emission Tomography scan using radio tracer MK-6240
    Other Name: tau PET
  • Behavioral: Neurocognitive testing
    A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.
  • Other: MRI
    High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.
Study Arms  ICMJE
  • Experimental: Age 60-65 ApoE e4+
    Participants in this cohort are between the ages of 60-65 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
  • Experimental: Age 66-70 ApoE e4-
    Participants in this cohort are between the ages of 66-70 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
  • Experimental: Age 66-70 ApoE e4+
    Participants in this cohort are between the ages of 66-70 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
  • Experimental: Age 71-75 ApoE e4-
    Participants in this cohort are between the ages of 71-75 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
  • Experimental: Age 71-75 ApoE e4+
    Participants in this cohort are between the ages of 71-75 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
  • Experimental: Age 76-80 ApoE e4-
    Participants in this cohort are between the ages of 76-80 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
  • Experimental: Age 76-80 ApoE e4+
    Participants in this cohort are between the ages of 76-80 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
  • Experimental: Age 81-85 ApoE e4-
    Participants in this cohort are between the ages of 81-85 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
  • Experimental: Age 81-85 ApoE e4+
    Participants in this cohort are between the ages of 81-85 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.
    Interventions:
    • Radiation: Amyloid PET scan
    • Drug: Tau PET scan using MK-6240
    • Behavioral: Neurocognitive testing
    • Other: MRI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 28, 2019)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 22, 2024
Estimated Primary Completion Date December 22, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Between the ages of 60 and 85;
  2. Speaks fluent English;
  3. Visual and auditory acuity adequate for neuropsychological and computerized testing;
  4. Good general health with no disease(s) expected to interfere with the study;
  5. Willing and able to participate for the duration of the study and in all study procedures including MRI and PET;
  6. Normal cognition defined as a Clinical Dementia Rating of 0 and a Mini-Mental State Examination score of 27 or higher.

Exclusion Criteria:

  1. Significant co-morbid neurologic disease such as Parkinson's disease, multiple sclerosis, brain cyst, tumor or aneurysm;
  2. Major health conditions such as uncontrolled diabetes mellitus, uncontrolled hypertension, nutritional deficiency or uncontrolled thyroid disease;
  3. Significant psychiatric disorders such as schizophrenia, bipolar disorder, anxiety disorder, major depressive disorder, or attention-deficit hyperactivity disorder;
  4. ADRC consensus diagnosis of dementia or mild cognitive impairment;
  5. Cognitive impairment when tested at baseline (defined as a score on any neuropsychological test of 1.5 SDs or more outside the age norm);
  6. Alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria);
  7. MRI contraindications, e.g. pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body. Females who are pregnant or trying to get pregnant are also excluded;
  8. PET contraindications, e.g. significant prior radiation exposure and pregnancy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Martina K Hollearn, BA 949-824-7463 mhollear@uci.edu
Contact: Blake A Miranda, BS 949-824-0904 bamirand@uci.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03860857
Other Study ID Numbers  ICMJE 2017-3832
R01AG053555-02 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michael Yassa, University of California, Irvine
Study Sponsor  ICMJE University of California, Irvine
Collaborators  ICMJE National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Michael A Yassa, PhD University of California, Irvine
Study Director: Liv C McMillan, BS, CCRP University of California, Irvine
PRS Account University of California, Irvine
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP